Department of Cardiology III, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
Department of Cardiology III, Cangzhou Central Hospital, Cangzhou, Hebei Province, China.
Int J Cardiol. 2021 Sep 1;338:176-184. doi: 10.1016/j.ijcard.2021.05.044. Epub 2021 Jun 1.
Long non-coding RNA (lncRNA) is crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA PART1 on myocardial ischemia-reperfusion (I/R) injury by targeting BIRC5 through miR-503-5p pathway.
I/R model was created in vivo and vitro. The level of gene and protein was detected by RT-PCR and western blot. The apoptosis level was assessed by TUNEL and flow cytometry. Cell viability was determined by MTT. Mitochondrial function was evaluated by ATP content, ROS production, GSH level, and mitochondrial membrane potential. Cardiac function was confirmed by echocardiography, TTC staining, and H&E staining.
Here, we found that the expression of lncRNA PART1 was down-regulated in the I/R hearts and H/R cardiomyocytes. Forced expression of PART1 remitted cardiac I/RI and H/R cardiomyocyte injury. Silencing of PART1 aggravated apoptosis and mitochondrial damage in cardiomyocytes. We found that PART1 functioned as a competing endogenous RNA of miR-503-5p, which decreased the expression of miR-503-5p. We further established BIRC5 as a target of miR-503-5p. Furthermore, PART1 prevented apoptosis and improved mitochondrial function in myocardial I/RI by targeting miR-503-5p/BIRC5.
In summary, PART1 protected mitochondrial function via miR-503-5p/BIRC5 pathway in MI/RI, which may provide the new theoretical basis for MI/RI treatment in the clinic.
长链非编码 RNA（lncRNA）对于心脏发育以及成年心脏结构维持和功能至关重要。在此，我们通过 miR-503-5p 通路靶向 BIRC5 研究了 lncRNA PART1 对心肌缺血再灌注（I/R）损伤的影响。
在体内和体外建立 I/R 模型。通过 RT-PCR 和 Western blot 检测基因和蛋白水平。通过 TUNEL 和流式细胞术评估细胞凋亡水平。通过 MTT 测定细胞活力。通过 ATP 含量、ROS 产生、GSH 水平和线粒体膜电位评估线粒体功能。通过超声心动图、TTC 染色和 H&E 染色确认心脏功能。
在这里，我们发现 lncRNA PART1 在 I/R 心脏和 H/R 心肌细胞中的表达下调。PART1 的强制表达可减轻心脏 I/RI 和 H/R 心肌细胞损伤。PART1 的沉默加重了心肌细胞中的细胞凋亡和线粒体损伤。我们发现 PART1 作为 miR-503-5p 的竞争性内源性 RNA 发挥作用，降低了 miR-503-5p 的表达。我们进一步确定 BIRC5 是 miR-503-5p 的靶标。此外，PART1 通过靶向 miR-503-5p/BIRC5 防止心肌 I/R 中的细胞凋亡并改善线粒体功能。
总之，PART1 通过 miR-503-5p/BIRC5 通路在 MI/RI 中保护线粒体功能，这可能为 MI/RI 的临床治疗提供新的理论基础。
